Journal of the American Chemical Society, Vol.136, No.2, 741-749, 2014
Circular Permutation of a WW Domain: Folding Still Occurs after Excising the Turn of the Folding-Nucleating Hairpin
A hyperstable Pin1 WW domain has been circularly permuted via excision of the fold-nucleating turn; it still folds to form the native three-strand sheet and hydrophobic core features. Multiprobe folding dynamics studies of the normal and circularly permuted sequences, as well as their constituent hairpin fragments and comparable-length beta-strand-loop-beta-strand models,. indicate. 2-state folding for all topologies. N-terminal hairpin formation is the fold nucleating event for the wild-type sequence; the slower folding circular permutant has a more distributed folding transition state.